1. Field of the Invention
The present invention concerns an improved injectable formulation of the drug disulfiram, for use in the treatment of alcoholism.
2. Brief Description of the Prior Art
Disulfiram (DSF) is a drug widely used in the treatment of alcoholism. Anyone who consumes ethyl alcohol after pretreatment with DSF (taken orally) will experience the subjectively unpleasant Disulfiram-Ethanol Reaction (DER) characterized by nausea, palpitations, flushing, hyperventilation and hypotension. In theory, treatment of an alcoholic patient with DSF should discourage a relapse into impulsive drinking. In practice, DSF therapy often ends in failure when the patient stops taking the drug and resumes drinking after the effects have worn off. An alternative approach, parenteral therapy with subcutaneous implants of sterile DSF tablets has been widely practiced for many years but it is now clear that these implants are inactive placebos which can not elicit a true DER in alcoholic humans. Alcoholics implanted with DSF tablets do not experience a DER after drinking alcohol, nor do they drink significantly less alcohol than those implanted with an inactive placebo. These failures of therapy are probably due to subtherapeutic dosage as well as the poor bioavailability of DSF tablets in the subcutaneous milieu where they often become encapsulated by fibrotic tissue. The following references describe relevant prior art methods: Bergstrom et al., Lancet 1:49-50, 1982; Kline and Kingstone, Can Med Assoc. J. 116:1382-1383, 1977; Lewis et al., Can Psychiatr. Assoc J. 20:283-286, 1975.
Detoxification of an alcoholic induces a remission of the disease which may be followed by an acute relapse into abusive drinking at any time; treatment with an effective sustained-release formulation of DSF is likely to prolong the duration of the initial remission and lengthen the period between subsequent relapses.
The present invention relates to an effective injectable formulation of DSF wherein the drug is released in a sustained manner over a period of several weeks.